Safety and Efficacy Study of Icotinib With Intensity-modulated Radiotherapy in Nasopharyngeal Carcinoma

Phase Ⅰ/Ⅱ Study of Icotinib Hydrochloride Combined With Intensity-modulated Radiotherapy in Nasopharyngeal Cancer

Nasopharyngeal carcinoma (NPC) is a prevalent disease in southeast of China. Radiation therapy with or without chemotherapy is a standard therapy for nasopharyngeal cancer. Cytotoxic chemotherapy plays an important role in the curative treatment of advanced NPC. However, concurrent chemoradiotherapy increased significantly local and systemic toxic effects, which may preclude many patients from proceeding with combined therapy. The epidermal growth factor receptor(EGFR) gene is amplified in 40% and EGFR protein is overexpressed in over 80% of NPC. EGFR overexpression is also associated with shorter survival following chemoradiotherapy in locoregionally advanced NPC. And some basic researches have proved that EGFR tyrosine kinase inhibitors(TKIs) could increase the radiosensitivity and reduce the epithelial-mesenchymal transition (EMT) in NPC cell line. Moreover, distant metastases has been the major cause of treatment failure in NPC. Icotinib hydrochloride is a novel oral EGFR TKIs with low mammalian toxicity(made in China). But base on toxic effects of Icotinib, it may increase toxic effects about skin and mucosa in combination therapy with Icotinib and Intensity-modulated Radiotherapy (IMRT). The prospective study will assess the tolerability and efficacy of Icotinib combined with IMRT in patients with NPC. This regimen is of great interest and it has potential to alleviate the adverse effects, improve patient compliance and better therapeutic ratio.

Study Overview

• Status: Completed
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Drug: Icotinib; Radiation: intensity-modulated radiotherapy; Drug: Paclitaxel and Cisplatin; Other: Quality of life; Genetic: Epidermal growth factor receptor status

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Taizhou, Zhejiang, China, 317000
      • Taizhou Hospital, Wenzhou Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with histological proof of squamous carcinoma of the nasopharynx.
2. Patients must have ECOG Performance Status of 0-1.
3. Patients should have adequate bone marrow function defined as an absolute peripheral granulocyte count (AGC) of >/= 1500 cells/mm3, platelet count of >/= 100,000 cells/mm3; adequate hepatic function with bilirubin </= 1.5mg/dl, AST and ALT </= 2x the upper limit of normal; serum creatinine </= 1.5mg/dl, creatinine clearance >/= 50 ml/min and INR 0.8 - 1.2.
4. Patients must sign a study specific informed consent form prior to study entry.

Exclusion Criteria:

1. Evidence of metastases by clinical or radiographic examinations.
2. History of malignancy other than non-melanoma skin cancer.
3. Prior chemotherapy or anticancer biologic therapy for any type of cancer, or prior radiotherapy to the head and neck region except for radioactive iodine therapy.
4. Patients with uncontrolled intercurrent disease.
5. Patients with currently active malignancy.
6. Pregnant or lactating women Female patients of childbearing potential who are unwilling to practice adequate contraception during study treatment and for two months after the last administration of study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Phase I: the maximum tolerated dose of Icotinib in combination with IMRT for NPC	30 days
Phase II: 2 years locoregional control rate	Two years

Secondary Outcome Measures

Outcome Measure	Time Frame
The overall response rate (complete and partial response)	1 month following treatment and then every 3 months
The acute and late toxicity profile associated with the study regimen	1 month following treatment and then every 3 months
The duration of control of locoregional disease	1 month following treatment and then every 3 months
Overall survival, disease-free survival, and distant relapse rates	At time of locoregional disease progression
EGFR status in tissue and blood before treatment	2 week of pretreatment

Collaborators and Investigators

• Sponsor: Taizhou Hospital
• Investigators: Study Director: Haihua Yang, MD., Department of Radiation Oncology, Taizhou Hospital, Wenzhou Medical College.; Study Chair: Wei Hu, MD., Department of Radiation Oncology, Taizhou Hospital, Wenzhou Medical College.; Principal Investigator: Wei Wang, BS, Department of Radiation Oncology, Taizhou Hospital, Wenzhou Medical College.; Principal Investigator: Chao Zhou, MD., Department of Radiation Oncology, Taizhou Hospital, Wenzhou Medical College.

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: February 13, 2012
• First Submitted That Met QC Criteria: February 15, 2012
• First Posted (Estimate): February 16, 2012

Study Record Updates

• Last Update Posted (Actual): April 17, 2018
• Last Update Submitted That Met QC Criteria: April 16, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Icotinib; nasopharyngeal carcinoma(NPC); Intensity Modulation Radiation Therapy(IMRT)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Cisplatin; Mitogens
• Other Study ID Numbers: YHH-201201